Researchers Shed Light on Asthma's Mysteries

New Findings on a Particularly Confusing Form of the Lung Disease

Researchers are making interesting new discoveries about a particularly confusing type of asthma.

Doctors increasingly are recognizing that as many as half of asthma sufferers have a form of the lung disease known as nonallergic asthma. Some medications that help control symptoms of the more familiar allergic asthma aren't as effective in nonallergic patients.

There is still much that isn't understood about allergic asthma, which is brought on by an overactive response of the body's immune system to food, pollen and other allergens. Even more mysterious is the cause of nonallergic asthma, which doesn't involve an immune-system response. Symptoms for both forms of the disease typically include constricted airways, wheezing and coughing.

Researchers also continue to discover substances in the environment that appear to increase the risk for developing asthma. One of the latest studies, from New York's Columbia University Medical Center, found an association between asthma rates and phthalates, chemicals used in many plastic products that have raised health concerns.

The scientific hunt for the causes of asthma reflects concern about the puzzling rise in rates of the disease. In the U.S., the percentage of the population diagnosed increased in 2010 to 8.4%—or more than 25 million adults and children—from 5.5% in 1996, according to the most recent data from the Centers for Disease Control and Prevention. Some 1.8 million people visited a hospital emergency department in 2010 for asthma-related treatment.

Scientists studying nonallergic asthma say greater understanding of the molecular pathways in this form of the disease could lead to new targets for drug development.

Stefan Worgall, chief of the pediatric pulmonology, allergy and immunology division at Weill Cornell Medical College, and his colleagues recently discovered that when a normally occurring type of fat, known as sphingolipids, isn't embedded properly in the cell walls in the lungs of mice, the airways constrict.

In a related experiment, they administered a drug to inhibit sphingolipid production in tissue taken from a healthy human lung. The tissue showed the same type of constriction as seen in the mice, the study found. The report was published last year in the journal Science Translational Medicine.

Dr. Worgall says the finding could help explain why obesity is a risk factor for asthma. Obese people tend to exhibit abnormalities in sphingolipids, he says.

Currently, Dr. Worgall and his team are measuring sphingolipid levels in the blood and breath of asthmatic children. Early findings suggest the levels appear abnormal, he says.

Jeroen Douwes, director of the Centre for Public Health Research, at Massey University in New Zealand, believes nonallergic-asthma patients might have particularly sensitive nerves in the lungs that tell the brain at a lower-than-normal threshold that a noxious substance is in the air and airways need to be constricted.

Take a Breath

Asthma rates have been rising for years, for reasons that aren't understood.

About 8.4% of people in the U.S. had asthma in 2010, up from 5.5% in 1996.

Boys are more prone to asthma than girls. But as adults, more women have asthma than men.

Black children are twice as likely as white children to have asthma.

Symptoms of asthma can include coughing, chest tightness, wheezing and difficulty breathing.

Dust, mold, pets, exercise and strong emotions are some common triggers of asthma attacks.

—Source: CDC

Some previous studies suggest some asthmatics have an inappropriate neural response, which might translate into greater sensitivity, says Dr. Douwes. He is currently reanalyzing samples from previous studies of children followed since birth for asthma and allergy symptoms to look for evidence of neural activation.

An oversensitive neural pathway would help explain such mysteries as why dust or pollen can trigger an asthma attack without causing an allergic reaction and why stress has been found to bring on attacks in some people, Dr. Douwes says.

Not all asthmatics respond to traditional asthma medications. Corticosteroids, such as prednisone, for instance, are usually administered with an inhaler and in other forms to prevent asthma attacks. The drug is generally effective in people with allergic asthma because it dampens the body's immune response to an allergen. People with nonallergic asthma often get less relief from corticosteroids. Instead, these patients might be given another type of drug called a beta-agonist, such as albuterol and levalbuterol, which works by relaxing lung muscles.

Dr. Douwes says some medical professionals also have found that people with nonallergic asthma seem to respond well to anticholinergic drugs, which target neural pathways. Among such drugs are Atrovent and Oxivent.

"That means we've got another potential drug that could be used, particularly for those asthmatics where traditional treatment isn't as effective as it should be," he says.

Environmental factors are among the most studied causes for both types of asthma. In a recent study of phthalates, researchers studied 300 women and their children living in New York's inner city, where asthma rates are relatively high. The study measured phthalate levels in the women's urine during pregnancy and in the children at ages 3, 5 and 7 years old.

After taking into account other risk factors, such as maternal smoking, the researchers found significantly higher rates of asthma among the children whose mothers had the greatest levels of phthalates during pregnancy, says Rachel Miller, a co-author of the study and an allergist, pulmonologist and environmental health sciences professor at Columbia University Medical Center.

But there wasn't a correlation between asthma and the children's own exposure to phthalates in the early years after birth, according to the study, which was published in the journal Environmental Health Perspectives in September.

"It's assumed that the prenatal period is going to be your most susceptible period [for disease], including lung development," says Robin Whyatt, a study co-author and a professor of environmental health sciences at Columbia's Mailman School of Public Health. The researchers cautioned that while the study found an association between phthalates and asthma, it didn't prove causation.

The finding is "potentially very important because exposure to phthalates is widespread," says Neil Pearce, a professor of epidemiology and biostatistics at the London School of Hygiene and Tropical Medicine, who studies asthma but wasn't involved in the phthalate study.

The CDC says people are widely exposed to phthalates but the chemical's impact on human health isn't known and needs more research. Phthalates have been found to affect the reproductive systems of lab animals, according to the CDC.

Phthalates, which make plastics flexible, among other functions, are found in many household products from vinyl flooring to certain types of plastic food containers and scented candles, but aren't listed on labels. Dr. Whyatt says that to minimize phthalate exposure, people shouldn't microwave in plastic containers and should store food in glass instead.